Human and mouse homologs of the Saccharomyces cerevisiae RAD54 DNA repair gene: Evidence for functional conservation

Background: Homologous recombination is at eminent importance both in germ cells, to generate genetic diversity during meiosis, and in somatic cells, to safeguard DNA:rom genotoxic damage. The genetically well-defined RAD52 pathway is required for these processes in the yeast Saccharomyces cerevisiae, Genes similar to those in the RAD52 group have been identified in mammals. Ii is not known whether this conservation of primary sequence extends to conservation of function. Results: Here we report the isolation of cDNAs encoding a human and a mouse homolog of RAD54. The human (hHR54) and mouse (mHR54) proteins were 48% identical to Rad54 and belonged to the SNF2/SWI2 family, which is characterized by amino-acid motifs found in DNA-dependent ATPases. The hHR54 gene was mapped to chromosome 1p32, and the hHR54 protein was located in the nucleus. We found that the levels of hHR54 mRNA increased in late G1 phase, as has baeri found for RAD54 mRNA. The level of mHR54 mRNA was elevated in organs of germ cell and lymphoid development and increased mHR54 expression correlated with the meiotic phase of spermatogenesis. The hHR54 cDNA could partially complement the methyl methanesulfonate-sensitive phenotype oi SI cerevisiae rad54 Delta cells. Conclusions: The tissue-specific expression of mHR54 is consistent with a role for the gene in recombination, The complementation experiments show that the DNA repair function of Rad54 is conserved from yeast to humans, Our findings underscore he fundamental importance of DNA repair pathways: even though they are complex and involve multiple proteins, they seem to he functionally conserved throughout;he eukaryotic kingdom.